The delivery of a therapeutically active compound (i.e., a drug) to a living organism is generally affected by a number of parameters beyond the actual chemical identity and pharmacological activity of the drug.
Medicinal aerosols can be an effective way to introduce a drug into the pulmonary system via oral or nasal inhalation, but there are a number of important parameters governing medicinal aerosol compositions that affect their performance. The relative importance of these parameters can vary depending on the type of dosage form used (e.g., metered dose inhaler or MDI, dry powder inhaler, nebulizer) and the type of drug being delivered, but will usually include such things as the concentration of drug in the dosage form, the particle size of the aerosol that is delivered to an organism, the physicochemical stability of the composition, and the ability of particles delivered to the pulmonary system to be absorbed by the body.
In order to achieve certain desirable properties or an acceptable balance of properties it is sometimes desirable to incorporate various excipients into a medicinal aerosol composition. As used in this application, an “excipient” refers broadly to any formulation additive other than the primary active drug moiety used to improve some aspect of the formulation. Many different excipients have been suggested for use in medicinal aerosols, for such things as solubilizing drug, physically stabilizing or dispersions of drug particles, increasing the emitted particle size, and so on. But many proposed excipients, while perhaps providing one or more benefits, suffer from drawbacks that make them otherwise undesirable for use, such as toxicological problems, manufacturing difficulties, limited solubility or detrimental interactions with other product components. Hence, there is an ongoing need for new and effective excipients that are useful in medicinal aerosols, particular pressurized medicinal aerosols using hydrofluorocarbon propellants, such as HFC-134a and HFC-227. Although tremendous research investment has been made over the last decade, formulating CFC-free pressurized metered dose inhalers that are suitable in terms of the stringent functional and therapeutic requirements today continues to be of major importance.